A genotyping study of 13 cases of early-onset Charcot-Marie-Tooth disease / 中国当代儿科杂志

OBJECTIVE@#To study the clinical characteristics and genetic variation of early-onset Charcot-Marie-Tooth disease (CMT).@*METHODS@#Children with a clinical diagnosis of early-onset CMT were selected for the study. Relevant clinical data were collected, and electromyogram and CMT-related gene detection were performed and analyzed.@*RESULTS@#A total of 13 cases of early-onset CMT were enrolled, including 9 males (69%) and 4 females (31%). The mean age at consultation was 4.0±2.1 years. Among them, 12 children (92%) had an age of onset less than 2 years, 9 children (69%) were diagnosed with CMT type 1 (including 6 cases of Dejerine-Sottas syndrome), 1 child (8%) with intermediate form of CMT, and 3 children (23%) with CMT type 2. The genetic test results of these 13 children showed 6 cases (46%) of PMP22 duplication mutation, 3 cases (23%) of MPZ gene insertion mutation and point mutation, 3 cases (23%) of MFN2 gene point mutation, and 1 case (8%) of NEFL gene point mutation. Eleven cases (85%) carried known pathogenic mutations and 2 cases (15%) had novel mutations. The new variant c.394C>G (p.P132A) of the MPZ gene was rated as "possibly pathogenic" and the new variant c.326A>G (p.K109R) of the MFN2 gene was rated as "pathogenic".@*CONCLUSIONS@#Early-onset CMT is mainly caused by PMP22 gene duplication mutation and MPZ gene mutations. The clinical phenotype is mainly CMT type 1, among which Dejerine-Sottas syndrome accounts for a considerable proportion.

Efficacy of chemotherapy using 10-hydroxycamptothecin on recurrent or refractory neuroblastoma in children / 中国当代儿科杂志

<p><b>OBJECTIVE</b>The patients with recurrent or refractory neuroblastoma have a very poor prognosis and high mortality. 10-hydroxycamptothecin (HCPT) is a new agent extracted from comptotheca acuminate, a native plant. It has been shown to be very effective in some solid tumors such as gastric and colon cancers, lung cancers and ovary cancers. However, its efficacy in neuroblastoma has not been determined. This study aimed to investigate the therapeutic effects of HCPT in the treatment of recurrent or refractory neuroblastoma in children.</p><p><b>METHODS</b>Ten children with recurrent neuroblastoma and two children with refractory neuroblastoma were treated with HCPT. Of them, 5 children with recurrent neuroblastoma were treated with HCPT alone, and the other 7 patients received combination chemotherapy of HCPT plus other agents. The HCPT alone treatment group was injected with HCPT (7.5 mg/m2 daily) for 14 consecutive days. The combination chemotherapy group was alternately treated with the modified new protocol A1 (cyclophosomide 1 200 mg/m2 on day 1, etoposide 100 mg/m2 on days 1-5, HCPT 5 mg/m2 on days 1-3, cisplatin 90 mg/m2 on day 4) and the modified protocol B (ifosfomide 1.5 g/m2 on days 1-5, HCPT 5 mg/m2 on days 1-3, carboplatin 450 mg/m2 on day 2).</p><p><b>RESULTS</b>Four patients (33.3%) achieved partial remission and 8 patients (66.7%) had stable disease. The median remission duration was 3.5 months (2-5 months). HCPT treatment as a single agent resulted in mild side effects. Myelosuppression and digestive disorders were found as the main adverse events in the combined chemotherapy group. No chemotherapy related deaths were found.</p><p><b>CONCLUSIONS</b>HCPT is safe and effective in the treatment of recurrent or refractory neuroblastoma. The toxicities of HCPT are tolerable. The long-term efficacy of HCPT warrants further research.</p>

Thyrotropin receptor gene inactivating mutation in Chinese children with congenital hypothyroidism / 中华儿科杂志

<p><b>OBJECTIVE</b>The inactivating mutation of thyrotropin receptor (TSHR) gene results in partial or complete insensitivity of thyrotropin (TSH) and dysfunction of the TSH-TSHR-cAMP cascade. Therefore, it may cause congenital hypothyroidism (CH). Depending on the degree of impairment of TSHR function, patients can present with subclinical hypothyroidism at one extreme of the spectrum, or severe hypothyroidism at the other. This study aimed to understand the relation between inactivating mutations of TSHR gene and Chinese children with CH.</p><p><b>METHODS</b>(1) Seventy-nine Chinese children with CH, including 14 subclinical hypothyroidism patients (8 boys and 6 girls, age 1 - 5.5 years) and 65 hypothyroidism patients (27 boys and 38 girls, age 1.5 - 6 years) were enrolled in this study. Meanwhile, 100 normal children were enrolled as control, 40 were male and 60 were female. The age of the normal children were at a range of 1 - 8 years. (2) Total genomic DNA was extracted from peripheral blood leukocytes of the 79 patients and 100 normal subjects. Exons 1 - 10 of TSHR gene were individually amplified by polymerase chain reaction (PCR) and mutations were detected by direct sequencing.</p><p><b>RESULTS</b>(1) A compound heterozygous missense mutations (Pro52Thr/Val689Gly) and a heterozygous missense mutation (Gly245Ser) were detected in 79 patients. The mutations of Pro52Thr and Gly245Ser were located within the extracellular domain of TSHR, while Val689Gly was located within the intracellular domain of TSHR. In 30 patients the normal cytosine at position 2181 in exon 10 was replaced by a guanine (GAC-->GAG), resulting in the replacement of Glu(727) by Asp. In 47 patients, the normal thymidine at position 561 in exon 7 was replaced by a cytosine (AAT-->AAC). This substitution did not change the amino acid (Asn) at position 187. (2) In 33 normal children the normal cytosine at position 2181 in exon 10 was also replaced by a guanine (GAC-->GAG) and in 50 normal children the normal thymidine at position 561 in exon 7 was replaced by a cytosine (AAT-->AAC).</p><p><b>CONCLUSIONS</b>Three heterozygous missense mutations (Pro52Thr, Gly245Ser, Val689Gly) of TSHR gene were firstly detected in Chinese children with CH. There was a polymorphism in exon 10 at nucleotide 2181 (GAC-->GAG) and in exon 7 at nucleotide 561 (AAT-->AAC) in TSHR gene. The inactivating mutation of TSHR gene is an infrequent pathogeny for CH.</p>